Evidence from skewed X inactivation for trisomy mosaicism in Silver-Russell syndrome.
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The finding of maternal uniparental disomy for chromosome 7 (matUPD7) in approximately 7% of Silver-Russell syndrome (SRS) cases has lead to the assumption that imprinted gene(s) on chromosome 7 are responsible for at least some cases. However, the observation in a familial case that both maternal and paternal inheritance of proximal 7p results in an SRS-like phenotype suggests that the causative genes may not be imprinted, and that an extra copy of genes within this region cause SRS. As all cases of complete matUPD7 could have arisen by trisomy rescue, it is possible that undetected trisomy 7 mosaicism contributes towards the phenotype of SRS, and that the matUPD7 seen in some cases is a consequence of trisomy rescue. Previous studies in cases of trisomy rescue for a number of autosomes have shown a strong association with skewed X inactivation in diploid tissues. Thus, we hypothesised that if trisomy mosaicism was involved in SRS, the frequency of skewed X inactivation should be increased in a population of non-matUPD7 SRS patients. Consistent with this hypothesis, results showed a significant increase in the frequency of completely skewed X inactivation in SRS patients (three of 29) when compared to controls (three of 270), suggesting the possible presence of undetected trisomy 7 in SRS patients and/or their placentas. (+info)
Cephalometric measurements and facial deformities in subjects with beta-thalassaemia major.
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This study was performed to identify cephalometric and facial features of patients with beta-thalassaemia major. A total of 54 thalassaemic subjects were examined for craniofacial deformities, including 37 patients (24 males and 13 females, aged 5-16 years) who had lateral cephalometric radiographs. The thalassaemic groups were compared with a normal control group matched for sex and dental age, using a t-test. All thalassaemic patients had a Class II skeletal base relationship. The average ANB angle was significantly larger than the controls in dental stages 2 and 3 (P < 0.05). Mandibular base length (Ar-Gn) was significantly less in thalassaemic patients than in controls, with the greatest differences (P < 0.001) found in the younger age group. The maxilla was of normal length (PNS-ANS, Ptm'-ANS') and appeared prominent (3.3 mm in males and 5.1 mm in females) due to a reduced cranial base length (Ar'-S') and a short mandible (Ar'-P'). Vertically, thalassaemic patients showed a significantly increased maxillary/mandibular planes angle in all groups, with differences ranging between 6.19 and 12.55 degrees (P < 0.001). Thalassaemic patients also showed a reduced posterior facial height (S-Go, Ar-Go) and increased anterior facial proportions. Of the 54 thalassaemic patients examined, 17 per cent had severe facial disfigurements (grade 3). (+info)
Lack of expression of XIST from a small ring X chromosome containing the XIST locus in a girl with short stature, facial dysmorphism and developmental delay.
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A 46,X,r(X) karyotype was found in a three and a half year old girl with short stature, facial dysmorphism and developmental delay. The clinical findings were consistent with the phenotype described in a limited number of patients with small ring X chromosomes lacking the XIST locus, a critical player in the process of X chromosome inactivation. Surprisingly, in our patient, fluorescent in situ hybridisation demonstrated that the XIST locus was present on the ring X. However, expression studies showed that there was no XIST transcript in peripheral blood cells, suggesting that the ring X had not been inactivated. This was confirmed by the demonstration that both of the patient's alleles for the androgen receptor gene were unmethylated, and that both of the patient's ZXDA alleles were expressed. The active nature of the ring X would presumably result in overexpression of genes that may account for the developmental delay observed for the patient. Using polymorphic markers along the X chromosome, the ring X was determined to be of paternal origin with one breakpoint in the long arm between DXS8037 and XIST and one in the short arm in Xp11.2 between DXS1126 and DXS991. To attempt to determine why the XIST gene failed to be expressed, the promoter region was sequenced and found to have a base change at the same location as a variant previously associated with nonrandom X chromosome inactivation. This mutation was not seen in over one hundred normal X chromosomes examined; however, it was observed in the paternal grandmother who did not show substantial skewing of X chromosome inactivation. (+info)
Craniofacial and brain abnormalities in Laron syndrome (primary growth hormone insensitivity).
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OBJECTIVE: To investigate abnormalities in the craniofacial structures and in the brain in patients with Laron syndrome. DESIGN: Eleven patients with classical Laron syndrome, nine untreated adults aged 36-68 years and two children aged 4 and 9 years (the latter treated by IGF-I), were studied. METHODS: Magnetic resonance images of the brain were obtained in all the patients. One patient also underwent computed tomography. The maximal diameter of the maxillary and frontal sinuses was measured and compared with reference values, the size of the sphenoid sinus was evaluated in relation to the sella, and the mastoids were evaluated qualitatively (small or normal). The brain was evaluated for congenital anomalies and parenchymal lesions. RESULTS: In the adult untreated patients, the paranasal sinuses and mastoids were small; in six patients, the bone marrow in the base of the skull was not mature. The diploe of the calvaria was thin. On computed tomography in one adult patient, the sutures were still open. A minimal or mild degree of diffuse brain parenchymal loss was seen in ten patients. One patient demonstrated a lacunar infarct and another periventricular high signals on T2-weighted images. Two patients had cerebellar atrophy. CONCLUSIONS: The present study has demonstrated the important role IGF-I plays in the development of the brain and bony structures of the cranium. (+info)
Multiple pericallosal lipomas in two siblings with frontonasal dysplasia.
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We report cases of two siblings with frontonasal dysplasia (FND) associated with multiple pericallosal lipomas in almost similar locations. In each sibling two separate curvilinear pericallosal lipomas were present-one in relation to the posterior part of the corpus callosum and the other in relation to the rostrum. To our knowledge, multiple pericallosal lipomas in association with FND have not been described before. Pericallosal lipomas in cases of FND are of the tubulonodular type; they have been reported only in relation to the anterior part of the corpus callosum. (+info)
Two-dimensional ultrasound is accurate in the diagnosis of fetal craniofacial malformation.
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OBJECTIVE: To assess the accuracy of antenatal ultrasound in the diagnosis of craniofacial malformations and to compare two-dimensional with three-dimensional ultrasound. METHODS: This was a retrospective study in which the archives of our ultrasound laboratory were searched for cases with an ultrasound diagnosis of craniofacial malformation in the period 1986-2001. No attempt was made to look for false-negative diagnoses. RESULTS: Sixty cases with an antenatal diagnosis of a craniofacial malformation were found: 37 with cleft lip/palate; 17 with heterogeneous dysmorphisms (including mostly micrognathia and craniosynostosis) and 6 with miscellaneous craniofacial malformations. Associated anomalies were present in 48/60 (80%) cases, and holoprosencephaly (25 cases) was the most frequent of these. In 43 (72%) cases the diagnosis was made before 24 weeks' gestation. Postnatal follow-up was available for 43 cases and there was always complete correlation between antenatal and postnatal diagnoses. Cleft lip/palate was always accurately differentiated from cleft lip. Three-dimensional ultrasound was performed in 12 cases and was successful in 11. However, it did not provide further diagnostic information with regard to the two-dimensional scan. DISCUSSION: Current two-dimensional ultrasound in expert hands allows an accurate diagnosis of craniofacial abnormalities from early gestation. In our hands, three-dimensional ultrasound did not add any valuable diagnostic information. Three-dimensional ultrasound may facilitate the understanding of the lesion by the parents and facilitate communication with the plastic surgeons. However, these potential benefits need to be carefully weighed against the costs of the ultrasound instrumentation, increased examination time and training of personnel. (+info)
Sotos syndrome (cerebral gigantism): analysis of 8 cases.
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Sotos syndrome or cerebral gigantism is characterized by macrocephaly, overgrowth, mental retardation and central nervous system abnormalities. Congenital heart defects may be present. We report 8 patients with this syndrome and relate their clinical features, neuroimaging and echocardiographic findings. (+info)
Investigation of a cyclopic, human, term fetus by use of magnetic resonance imaging (MRI).
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Using magnetic resonance imaging (MRI), the internal neural and craniofacial malformations of a cyclopic fetus are described. External facial features were characterized by a tubular proboscis situated above a single eye slit. The brain was recognized as 'pancake' type alobar holoprosencephaly (a condition where the undifferentiated telencephalon partially surrounds a monoventricle). Displacement of some bones that normally contribute to the orbit could be clearly discerned. Absence of neural structures (e.g. falx cerebri, corpus callosum) and missing components of the ethmoid bone indicated a midline deficit. This correlates with proposed theories of cyclopic embryopathy, which suggest that the prechordal plate and the neural crest cells are affected during the third week of gestation in cyclopia. (+info)